Self-Assembling

Overview

Self-assembling peptides are short, synthetic peptides characterized by amphipathic sequences. These peptides are able to spontaneously self-assemble in the aqueous solution to form highly organized structures such as hydrogels. GenScript's Peptide Synthesis Services can provide Self-assembling peptides with:

In 3-D Cell Culture and Tissue Engineering

One of the most well studied self-complementary peptides is, RADA-16, an ionic self-complementary peptide that has been widely studied for various applications in biocompatible materials. Monomeric RADA-16 has a high propensity to self-assemble into a series of organized stable β-sheet superstructures. The addition of monovalent ion salts such as sodium chloride can promote the self-assembling process of RADA-16 to quickly form highly ordered structures, albeit slower than the natural self-complementary beta amyloid (1-42). These scaffolds are bioactive materials, which have been applied in 3-D cell culture, wound healing, and neurite and synapse growth.

Self-assembling peptides can form ideal matrices for mammalian cell attachment, since cell adhesion motifs like the well-known RGD can be easily mimicked by sequences such as RAD. Similarly, other cell motifs can be linked to these monomeric peptides, which can be assembled into specific scaffolds capable of attaching to specific cells. In one study it was found that the resulting scaffolds can support neuronal cell attachment, differentiation and extensive neurite outgrowth. Primary rat neurons can form active synapses on these scaffolds surface. Osteoblasts, like neurons were also able to proliferate, differentiate, and migrate when RADA scaffolds were coupled to biologically active motifs known to enhance bone growth.

In Drug Discovery and Drug Delivery

Self-assembling peptides have the potential to stabilize and release drug candidates. For example, variants on the self-assembling peptide, EAK16 have been reported as stabilizing the anticancer drug, ellipticine in in vitro cancer cell delivery.

RADA-16 peptides form highly hydrated hydrogels [up to 99.5% (wt/vol) water], with pore sizes between 5 and 200 nm in diameter, allowing for the entrapment and gradual release of small molecules and proteins. Epidermal Growth Factor (EGF) mixed with RADA-16 hydrogel has been found to accelerate wound healing due to the effective release of EGF. In addition, RADA peptides were capable of disrupting prion aggregation in prion infected hamster brains.

References

• Zhang S et al. Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proceedings of the National Academy of Sciences 1993, 90, 3334-3338.
• Schneider A et al. Self-Assembling Peptide Nanofiber Scaffolds Accelerate Wound Healing. Plos One 2008, 3.
• Zhang, S et al. Self-complementary oligopeptide matricies support mammalian-cell attachment. Biomaterials 1995, 16, 1385-1393.
• Holmes, TC et al. Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. Proceedings of the National Academy of Sciences of the United States of America 2000, 97, 6728-6733.
• Horii, A et al. Biological designer self-assembling peptide nanofiber scaffolds significantly enhance osteoblast proliferation, differentiation and 3-D migration. Plos One 2007, 2.
• Koutsopoulos, S et al. Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold. Proceedings of the National Academy of Sciences of the United States of America 2009, 106, 4623-4628.